tbuckley/cabot-search huggingface dataset:
Differential expression analysis of circRUNX1 in patients with early resected EGFR-mutant NSCLC.
Authors: Carlos Pedraz, Masaoki Ito, Ana Giménez-Capitán, Stavros Giannoukakos, Miguel Angel Molina Vila, Rafael Rosell
Journal: Journal of Clinical Oncology (2023)

8529 Background: In the ADAURA study, patients with stage IB-IIIA of resected EGFR mutated lung adenocarcinoma receiving adjuvant osimertinib had a 2-year survival of 89% versus 52% in the placebo group (p&lt;0.001), however, predictive markers of response and recurrence are still needed. Circular RNA (circRNA) is a type of RNA which forms a covalently closed continuous loop. Some circRNAs have been reported as essential for tumor cell proliferation through functions distinct from the canonical linear RNA. In this project, we studied circRNA expression levels in formalin-fixed paraffin-embedded (FFPE) lung tumor samples in order to explore potential biomarkers that could predict the benefit of adjuvant EGFR TKIs in EGFR-mutant NSCLC patients. Methods: FFPE tumor samples from patients with EGFR-mutant, stage I-IIIB NSCLC (n=79) were collected. RNA was purified using the High Pure FFPET RNA Isolation Kit (Qiagen) and quantified by Nanodrop 2000 (Thermo Scientific). A total of 250 ng of RNA were subjected to overnight hybridization and downstream nCounter processing (NanoString) following manufacturer’s instructions for our circRNA custom panel. Differential expression analysis was performed using Excel (Microsoft) and Prism GraphPad (Dotmatics) software. Results: Analysis of the 79 samples included in the study shown a cluster of 3 circRNAs significantly upregulated (p&lt;0.05 and &gt;2 fold-change) in EGFR mutation-positive NSCLC relapsing withing the 36 months after resection, including circRUNX1, circFUT8 and circAASDH. Disease-free survival (DFS) was significantly shorter for the subgroup of patients with high versus low circRUNX1 expression. Additional multivariate analysis identified circRUNX1 expression and tumor stage as the only statically significant prognostic factors (circRUNX1 hazard ratio = 4.480, confidence interval = 2.172-9.239, P &lt; 0.001; pathological stage hazard ratio = 2.237, confidence interval = 1.183- 4.231, P = 0.008). Conclusions: CircRUNX1 could be a novel biomarker to predict the benefit of adjuvant EGFR TKIs with regards to DFS in EGFR-mutant resected NSCLC patients.
Recommendations for medical cannabis use in cancer patients by US oncology fellows and the impact of receiving prior training.
Authors: Kian Tehranchi, Rushad Patell, Poorva Bindal, Laura E. Dodge, Jason Freed, Mary K. Buss, Mara A. Schonberg, Ilana Monica Braun, Deepa Rangachari
Journal: Journal of Clinical Oncology (2023)

11030 Background: Despite the rising use of medical cannabis, limited evidence informs the safety and efficacy of cannabis use in cancer patients. A national survey of oncology fellows found that fellows felt insufficiently informed to make clinical recommendations about cannabis. In this secondary analysis of that survey, we aimed to measure how frequently trainees recommend cannabis and determine factors that influence this practice. Given the lack of evidence, we hypothesized that fellows who had been trained in medical cannabis use would be less likely to recommend cannabis to their patients. Methods: An online survey assessing trainee practices on medical cannabis was sent to 155 oncology fellowship program directors between January - March 2021 and directors were asked to distribute it to their fellows. The primary outcome was the number of times oncology fellows recommended cannabis in the prior year. Log-binomial regression was used to calculate risk ratios (RR) and 95% confidence intervals (CI) to evaluate whether the number of cannabis recommendations varied by participant age, gender, legality of cannabis in the state of practice, and prior training in medical cannabis. Results: Nationally, 40 programs from 25 states participated, with 189 of 462 trainees across these programs responding (40% response rate). Twenty-two percent (95% binomial CI: 16.3-29.0%) of participants reported recommending medical cannabis to &gt;5 patients in the past year. Twenty-four percent (95% binomial CI: 18.4-30.5%) of participants had prior training in medical cannabis. Among participant characteristics, only prior training in medical cannabis was associated with recommending cannabis to &gt;5 patients (RR: 2.42; 95% CI: 1.39–4.20). Conclusions: Despite limited evidence to support medical cannabis use among cancer patients, one in five oncology fellows participating in our study recommended it to &gt;5 patients in the past year. Prior training was associated with doubling of rates of recommending medical cannabis in this group. It is thus of critical importance that fellowship training on this subject reflects best available evidence to guide trainees in well-informed decision-making. Factors associated with trainees recommending medical cannabis to &gt;5 patients. [Table: see text]
Real-world performance of a multi-cancer early detection test based on integrative analysis of cell-free DNA whole-methylome sequencing.
Authors: Yulong LI, Xiaofeng Song, Ning Shen, Yuanyuan Hong, Ying Yang, Yu S. Huang, Weizhi Chen
Journal: Journal of Clinical Oncology (2023)

10521 Background: Early detection and diagnosis is key to reducing cancer-related mortality. We developed a blood-based multi-cancer early detection test, called THEMIS, using multimodal analysis of plasma cell-free DNA (cfDNA) methylation, fragmentation, and copy number alteration features by whole-methylome sequencing (WMS). The real-world performance of THEMIS was investigated with a prospective cohort of high-risk populations and the preliminary results were reported here. Methods: A total of 1,374 adults over 65 y with additional cancer risk factors for five common cancers (colorectal, esophageal, liver, lung, or stomach cancer) were recruited in the city of Wuxi, Jiangsu province, China. Additional risk factors included fecal occult blood, smoking history, H. pylori infection, HBV infection, and serum protein biomarkers. Participants had no known cancer diagnosis at the time of administration. Blood samples were collected and subject to low-pass WMS assay (~2X) and cancer probability was predicted by the THEMIS model, which was developed and locked in previous studies. Participants predicted as cancer positive by THEMIS were followed up until positive cancer diagnosis in a clinic or one year after receiving the test report, whichever was earlier. Results: At a fixed cutoff rendering 99% training specificity, THEMIS predicted 58 (4.15%) positive cases, among whom 19 participants consented to and completed follow-up. Ten participants received confirmed cancer diagnosis within the follow-up period, including five lung cancers, three liver cancers, one esophageal cancer, and one colorectal cancer. These results yielded a positive predictive value (PPV) of 52.6%. Those who declined follow-up upon a positive THEMIS report were predicted with digestive tract cancers, which need gastrointestinal endoscope for diagnostic confirmation. Conclusions: The nonivasive blood-based THEMIS test demonstrated promising performance and patient compliance for clinical utility to detect cancer early and improve patient outcome. Given that clinical follow-ups were only conducted with a subset of participants, future investigations of the precise real-world performance of THEMIS are needed with more complete patient follow-up.
Social determinants of health as a primary driver in outcomes in acute myeloid leukemia: An urban academic center experience.
Authors: Ian Michael Bouligny, Graeme Murray, Tilak Patel, Michael Doyel, Josh Boron, Valerie Tran, Juhi Gor, Yiwei Hang, Thuy Ho, Kyle Zacholski, Chad Michael Venn, Yanal Mufeed Alnimer, Nolan Wages, Steven Grant, Keri Renee Maher
Journal: Journal of Clinical Oncology (2023)

e18659 Background: Healthcare disparities are pervasive in the treatment of cancer. Black patients with acute myeloid leukemia (AML) have shorter survival and inferior outcomes compared to White patients. Lack of insurance coverage decreases survival further. However, outcomes with respect to individual chemotherapy regimens remain unclear. Methods: We analyzed 306 patients with untreated AML that received front-line induction with an anthracycline and cytarabine (7+3) at VCU Massey Cancer Center between January 1, 2013 and January 1, 2022 in this single-center, retrospective analysis. We stratified patients into two cohorts: those that had private insurance or Medicare and those that had no insurance or Medicaid. We recorded baseline demographics, performance status, disease characteristics, response, receipt of allogeneic stem cell transplant (alloSCT), and survival. Patients who were alive at the end of the study period or were lost to follow-up were censored at the date of last contact. Results: There were 243 patients with private insurance or Medicare (Pi/M) and 63 patients with no insurance or Medicaid (Ni/M). The median age was 60 years (range, 18-77) in the Pi/M cohort and 52 years (range, 22-71) in the Ni/M cohort ( p &lt; 0.001). Most patients with private insurance or Medicare tended to be White (72.7% for Pi/M versus 36.1% for Ni/M, p &lt; 0.0001). There were no differences in sex (p = 0.778), the median ECOG score (1 versus 1, p = 0.096), or the median CCI score (4 versus 3, p = 0.607). There were no differences in the distribution of ELN 2017 risk, secondary AML ( p = 0.619), or procession to alloSCT ( p = 0.145). There was no difference in the composite complete remission (CRc; CR + CRi) rate between the Pi/M [44.5% (95% CI, 38.5-51.0)] and Ni/M cohorts (52.6% [95% CI, 39.9-65.0], p = 0.301). The median overall survival significantly favored the patients with private insurance or Medicare (21.7 months versus 15.2 months; log-rank, p = 0.030). Conclusions: AML patients with Medicaid or without insurance tend to be younger minorities. Despite no difference in fitness, disease characteristics, or even response to first-line chemotherapy, the median overall survival significantly favors patients with private insurance or Medicare. Our data clearly illustrates the primary role of social determinants of health in overall outcomes. Policymakers and physicians should push for improved access to care and more affordable insurance coverage. [Table: see text]
Association between excess body mass index trajectory and change in monoclonal protein level in patients diagnosed with monoclonal gammopathy of undetermined significance.
Authors: Lawrence Liu, Nikhil Grandhi, Mei Wang, Theodore Seth Thomas, Akhil Kumar, Kristen Marie Sanfilippo, Graham A. Colditz, Su-Hsin Chang
Journal: Journal of Clinical Oncology (2023)

10538 Background: Obesity is a known risk factor for the development of multiple myeloma (MM) and for progression of its asymptomatic premalignant state, monoclonal gammopathy of undetermined significance (MGUS) to MM. Prior studies have demonstrated that monoclonal protein (M-spike) at MGUS diagnosis as well as high M-spike velocity within a year following MGUS diagnosis predict progression of MGUS to MM, making M-spike a useful, readily available, and less invasive (compared to bone marrow biopsy) marker to assess progression risk. However, no studies have evaluated to what extent exposure to high body mass index (BMI) over time influences M-spike trajectory. Methods: Patients diagnosed with MGUS from 1999-2021 in the Veterans Health Administration were identified. We used a natural language processing-based algorithm to confirm MGUS diagnosis and progression to smoldering MM or MM. MGUS patients without IgM or IgD subtype or Diabetes Mellitus and were black or white were included in the analysis. Other exclusion criteria were progression within 5 years of MGUS diagnosis, patients without M-spike level within a year before or after MGUS diagnosis, and patients without BMI data 3 years or more after MGUS diagnosis. The exposure was the trajectory of excess BMI (defined as BMI &gt; 25 kg/m 2 ), defined by an area under the curve (AUC) of excess BMI during the 5 years following MGUS diagnosis. The outcome was continuous M-spike trajectory post-MGUS diagnosis since a prior study demonstrated that this was a reliable marker for progression risk A multivariable mixed model was used to estimate the association of excess BMI trajectory AUC with M-spike trajectory to control for correlation between M-spike values overtime. The covariates included BMI at MGUS diagnosis, M-spike level ( &gt; = 1.5g/dL) at MGUS diagnosis, age at MGUS diagnosis, sex, race, MGUS heavy chain subtype, and light-chain MGUS. Results: After applying the inclusion and exclusion criteria, the analytic cohort consisted of 6757 MGUS patients. Our multivariable analysis demonstrated a positive association between excess BMI trajectory and increasing M-spike trajectory (β = 0.005, p = 0.007). Conclusions: In patients diagnosed with MGUS, increasing BMI over time following MGUS diagnosis was associated with increasing M-spike level. This further supports the relationship between obesity and weight gain in the pathway of MGUS to MM progression.
Overall survival after the introduction of adjuvant treatment in stage III melanoma: A nationwide registry based study.
Authors: Hildur Helgadottir, Lars Ny, Gustav J. Ullenhag, Johan Falkenius, Rasmus Mikiver, Roger Olofsson Bagge, Karolin Isaksson
Journal: Journal of Clinical Oncology (2023)

9570 Background: Adjuvant treatments with PD-1 and BRAF+MEK inhibitors significantly prolong recurrence-free survival in stage III cutaneous melanoma. However, the effect on overall survival is still unclear. After the approval of adjuvant treatments with PD-1 inhibitors and BRAF+MEK inhibitors, based on recurrence-free survival data, these treatments have been widely implemented. However, there are significant side effects and costs of the treatment, and the overall survival effect remains a highly anticipated outcome. Methods: Clinical and histopathological parameters were obtained from the Swedish Melanoma Registry that covers nearly all (99%) primary cutaneous melanomas diagnosed. Information on deaths was received from the Cause of Death Registry, a virtually complete register of all deaths in Sweden. Patients diagnosed with stage III melanoma between 2016 and 2020 were included and divided depending on if they were diagnosed before or from July 2018, the timepoint when adjuvant treatment was introduced in Sweden (designated as pre- and post-cohorts). In Sweden, approved treatments are freely available for all residents and there is a high-adherence to national treatment guidelines. Data was retrieved for the age and sex of the patients, the site, histopathological subtype, Breslow thickness and ulceration of the primary melanoma, type of locoregional spread and numbers of affected lymph nodes. Patients were followed until the end of 2021. Melanoma-specific and overall survival were calculated using the Kaplan-Meier method and Cox regression analyses. Results: There were 1371 patients diagnosed with stage III melanoma in Sweden in 2016-2020. The median time of follow-up in the pre-cohort was 57 months (range 42-72 months) and in the post-cohort 27 months (range 12-42 months). The 2-year overall survival rates, comparing the 634 patients in the pre-cohort and the 737 in the post-cohort, were 84.3% (95% CI 81.4-87.3) and 86.1% (95% CI 83.4-89.0), respectively, with an adjusted HR 0.91 (95% CI 0.70-1.19, P= 0.51). Further, no significant overall or melanoma-specific survival differences were seen when comparing the pre- and the post-cohort in different subgroups depending on the age, sex or tumor characteristics. Conclusions: To our knowledge, this study is the first to assess the impact on overall survival from a national introduction of adjuvant treatment in stage III melanoma. In this nationwide, population and registry-based study, no survival benefit was detected in the cohort receiving adjuvant therapy. Considering also the significant side effects and costs, these findings encourage a careful assessment of the current recommendations on adjuvant treatment. To offer close follow-up, and only treat if relapse occurs, should be an option discussed with patients with fully resected stage III melanoma.
Rose geranium in sesame oil nasal spray to improve symptoms of nasal vestibulitis: A phase III double blinded randomized controlled trial.
Authors: Elizabeth Jane Cathcart-Rake, Paul J. Novotny, Deanne R. Smith, Susan E. Lewis-Peters, Karthik Giridhar, Kimberly O. Steinert, Darcie Dauer, Amanda K. O'Connor, Stephan Thome, Terra A. Register, Marsha K. Erickson, Bret Edward Buckley Friday, Charles L. Loprinzi
Journal: Journal of Clinical Oncology (2023)

12114 Background: A retrospective study suggested a potential benefit from rose geranium in sesame oil nasal spray for alleviating nasal vestibulitis symptoms in patients (pts) undergoing chemotherapy. Methods: Pts undergoing active chemotherapy who reported moderate or worse nasal symptoms were randomized 1:1 to receive a rose geranium in sesame oil nasal spray (RG) or an isotonic saline nasal spray (IS), administered twice daily for two weeks. Consenting pts completed nasal symptom questionnaires at baseline and then weekly while on treatment. The number and percentage of pts experiencing improvements in their nasal symptoms 2 weeks after initiating the nasal spray, defined as symptoms moderately (2) or very much (3) better on a 7-point global impression of change score (ranging from scores of -3: very much worse, to 3: very much better), was estimated within and then between each randomized arm, using Fisher’s exact test (5% significance level). The estimated odds ratio was determined (95% confidence interval). After 2 weeks, pts initially randomized to IS were allowed to cross-over to RG and completed weekly surveys. Results: 106 pts consented to this study; 43 pts in the RG arm and 41 in the IS arm were evaluable for the primary endpoint. Pts had a mean age of 57.8 (SD 13.9). Demographic characteristics and baseline nasal symptoms were similar between arms. The most prominent baseline nasal symptoms were dryness (36%) and bleeding (35%). Of the 43 evaluable pts who received RG, 67.4% reported improved nasal symptoms, compared with 36.6% of the 41 pts who received IS (p=0.009; Table). On the global impression of change score, pts who received RG had a mean score of 1.93 (SD 1.16), compared to a mean score of 0.98 (SD 1.41) among pts who received IS. Adjusting for potential confounding factors, pts who received RG had a 4.56 odds of responding to the nasal spray, compared with those who received IS (p=0.005). There were no significant differences between pt responses based upon type of nasal symptoms, age, allergies, or gender. Adverse events were sparse and did not differ between arms. 34 pts crossed over to RG after week 2. Among the 29 pts who completed final surveys, 37% reported a response on IS, 79% reported a response on RG. Conclusions: Rose geranium in sesame oil nasal spray significantly improves nasal vestibulitis symptoms among patients undergoing chemotherapy. Clinical trial information: NCT04620369 . [Table: see text]
The association between continuity of Medicaid enrollment and cancer survival in young adults diagnosed with cancer.
Authors: Kimberly J. Johnson, Derek J Brown, Allison A. King, Tess Thompson
Journal: Journal of Clinical Oncology (2023)

6538 Background: Disparities in young adult cancer survival between individuals with Medicaid and private insurance have been reported. To further understand the association between insurance-related access to healthcare and young adult cancer survival, we used Surveillance, Epidemiology, and End Results (SEER)-Medicaid linked data to test two hypotheses: 1) Those linked to Medicaid have lower cancer survival than those not linked, and 2) those with discontinuous enrollment in Medicaid around the time of diagnosis have lower survival than those with continuous enrollment. Methods: SEER-Medicaid linked data from 2006 to 2013 were obtained. Follow-up for vital status was through 2018. We included individuals diagnosed with a first malignant primary cancer diagnosed between 20 to 39 years. We excluded individuals who were linked to Medicaid enrollment records in multiple states during the same year. Individuals were defined as Medicaid-linked if they were linked to Medicaid in any U.S. state or the District of Columbia from 2006 to 2013. Medicaid enrollment was classified as continuous (enrolled within both the three months before and after diagnosis) and discontinuous (enrolled only within the 3 months before or after diagnosis or only at diagnosis). We used survival analysis methods including Kaplan-Meier (KM) curves and Cox Proportional Hazards (PH) regression models to evaluate survival differences in association with Medicaid linkage and enrollment timing after adjusting for race and a measure of census tract poverty. Results: Our analytic dataset included 137,259 young adults, among which there were 22,955 cancer deaths. KM curves showed consistently lower survival probabilities over time in young adults who linked vs. those not linked to Medicaid and in those with discontinuous vs. continuous enrollment (p &lt; .0001). Adjusted Cox PH regression models indicated that those who linked to Medicaid had a 2.19 (95% CI 2.14-2.25) times higher hazard of death vs. those who did not link. Those with continuous and discontinuous Medicaid enrollment had a 1.91 (95% CI 1.84 to 1.99) and 3.32 (95% CI 3.19 to 3.45) times higher hazard of death, respectively, vs. those not linked to Medicaid. Similar patterns were consistently observed for specific cancer types. Conclusions: These results confirm an insurance-associated disparity in a national sample of young adult cancer patients and provide additional information on risks in association with Medicaid enrollment continuity. These results further support the critical need for consistent health insurance coverage in young adults and for additional research to understand social, economic, and access-related factors leading to lower survival in the Medicaid population. Lowering administrative burdens for Medicaid enrollment, eligibility, and renewal are potentially important strategies for improving cancer outcomes.